{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:05:13Z","timestamp":1793639113285,"version":"4.5.1"},"reference-count":40,"publisher":"American Society of Hematology","issue":"11","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,9,11]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia. We present results from ELEVATE-TN after a median follow-up of 74.5 months. Overall, 535 patients were randomized (acalabrutinib-obinutuzumab, n = 179; acalabrutinib, n = 179; chlorambucil-obinutuzumab, n = 177). Median age was 70 years, 63.0% had unmutated immunoglobulin heavy chain variable region gene (uIGHV), 13.6% had del(17p) and\/or mutated TP53, and 17% had complex karyotype (CK; \u22653 chromosomal abnormalities). Median progression-free survival (PFS) was not reached (NR) for acalabrutinib-obinutuzumab and acalabrutinib vs 27.8 months for chlorambucil-obinutuzumab (both P &amp;lt; .0001); estimated 72-month overall PFS rates were 78.0%, 61.5%, and 17.2%, respectively. Acalabrutinib-obinutuzumab resulted in improved PFS vs acalabrutinib monotherapy (hazard ratio [HR], 0.58; P = .0229). Patients with uIGHV, del(17p) and\/or mutated TP53, or CK had significantly improved PFS with acalabrutinib \u00b1 obinutuzumab vs chlorambucil-obinutuzumab (P &amp;lt; .0001, P \u2264 .0009, and P &amp;lt; .0001 for both acalabrutinib-containing arms, respectively). Median overall survival (OS) was NR for all treatments, with significantly longer OS for acalabrutinib-obinutuzumab than chlorambucil-obinutuzumab (HR, 0.62; P = .0349). Estimated 72-month OS rates were 83.9%, 75.5%, and 74.7% for acalabrutinib-obinutuzumab, acalabrutinib, and chlorambucil-obinutuzumab, respectively. Adverse events (AEs) occurring after &amp;gt;4 years were mostly grade 1 to 2. Rates of AEs, serious AEs, and events of clinical interest were similar between acalabrutinib-containing arms and consistent with the known safety profiles of acalabrutinib and obinutuzumab. Efficacy and safety of acalabrutinib-containing arms were maintained, with longer PFS in both acalabrutinib arms than chlorambucil-obinutuzumab including in patients with high-risk features. This trial was registered at www.ClinicalTrials.gov as #NCT02475681.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024024476","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T16:10:50Z","timestamp":1744128650000},"page":"1276-1285","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":60,"title":["Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN"],"prefix":"10.1182","volume":"146","author":[{"given":"Jeff P.","family":"Sharman","sequence":"first","affiliation":[{"name":"1Willamette Valley Cancer Institute and Research Center, Eugene, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5513-5880","authenticated-orcid":false,"given":"Miklos","family":"Egyed","sequence":"additional","affiliation":[{"name":"2Department of Hematology, Somogy County M\u00f3r Kaposi General Hospital, Kaposv\u00e1r, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-8084","authenticated-orcid":false,"given":"Wojciech","family":"Jurczak","sequence":"additional","affiliation":[{"name":"3Department of Clinical Oncology, Maria Sk\u0142odowska-Curie National Research Institute of Oncology, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Skarbnik","sequence":"additional","affiliation":[{"name":"4Lymphoma and CLL Program, Novant Health Cancer Institute, Charlotte, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2446-098X","authenticated-orcid":false,"given":"Krish","family":"Patel","sequence":"additional","affiliation":[{"name":"5Swedish Medical Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6724-290X","authenticated-orcid":false,"given":"Ian W.","family":"Flinn","sequence":"additional","affiliation":[{"name":"6Tennessee Oncology, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1930-152X","authenticated-orcid":false,"given":"Manali","family":"Kamdar","sequence":"additional","affiliation":[{"name":"7University of Colorado Cancer Center, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-0769","authenticated-orcid":false,"given":"Talha","family":"Munir","sequence":"additional","affiliation":[{"name":"8Department of Haematology, Haematological Malignancy Diagnostic Service, St. James\u2019s Institute of Oncology, Leeds, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5693-2789","authenticated-orcid":false,"given":"Renata","family":"Walewska","sequence":"additional","affiliation":[{"name":"9Department of Haematology, Cancer Care, University 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